Oxybis



United States Patent 2,769,818 7 OXYBIS (PHENYLACETAMDES) Arthur H, Schlesinger, Dayton, =Ohio, assignor to Mon santo Chemical 'Company,St.-L'ouis, Mo., a corporation of Delaware N Drawing. Application December 7,1954, Serial N0.'"473,723

IZ'Claims. (01. 260-4473 The present inventionrelat'es to nitrogenous organic compounds and more particularly provides certain new and valuable 'diamido ethers and methods of -pre'paring the same.

According to the invention, a,a"'-oxybis EN-substituted]- aryl-aceta'mides are prepared by the -condensation of certain 'arylacetyl halides with certain amino compoundsh substantially according to the scheme:

in which R is selected from the class consisting of the .phenyl group :and acphenyl group-having:from l -to 2*subclass consisting ofhydrogen and Y, and further members in vvhieh YandY taken together yvithYNformalheterocyclic-ring structureof from 4--to 9 car'bon atdms which ring. structure is attached through saidN 'to the-remainder of the molecule of which -it forms apart. Acyl chlorides useful for. preparing tl1e diarnido ethers "include a-chlorophenylace ty'lchloride -'ani l derivatives I thereti f containing 1-or -2= cliloro-, nitro; or alkyl substituexits, e. g., a,4-'dichlorophenylacetyl chloride, u-chloro-iinitrophenylacetyl chloride, u,3,4-trichlorophenylacetyl chloride, a ch1oro-2,3-dinitrophenylacetyl chloride, (1,3- d-ichloro l-riitrophenylacetyl chloride, 0t-Ch101O-2-, or 3-, 4-tolylacetyl achlor ide, ---ot-ehloro-3-iseproplyphenylacetyl chloride, a-ehloro-4-tert-butylphenylacetyl chloridemx- "chloro-4-n-arnylphenylacetyl --chloride, "u chloro 2 j3 'tlimethylphenylacetyl chloride, 6,3 dichloro-4-n butylphenylacetyl chloride, a-chloro-4-nitro-2an;propylphenylacetyl 'liloricie, bg hdi'chl'tfm i tolylactyl'chloride, tc.

On'eeiass 6f amines which react with 'a-ehlorofihenyl acetyl chloride ortlie' aIky1-,chlof0- and/0r iiitro derivw tives thereof are hydrocarbonvamines having from 1 to 2 hydrocarbon-radicals of from 1 to 12: carbon atoms-each at tached' to the amino nitrogen atom. The hydrocarbon amine, whetherfprimary or secondary, may bealiphatic, cyeloaliphatic, aromatic, or ofhdth=a1iphatieand aroma-tic character, either substituted or unsubstituted. lExamples of presentlysuitable hydrocarbon amines are:

Ethylamine r Dimethylamine N-methylethylamiine Di: bpylami'ne lsobutylamine Di-n-amylamine N-ethyl-n'octylamine n-Hexylamine Didodecylamine N-butyl-n-decylamine .Diallylamine N-methyllalylamine Di-Lbu-tenylamine .Dil dodecenylamine 10 1 Dicyclohex-ylamine Cyclopentylamine N-ethylcyclohexylamine N-butyl-4-methy1cyclopentylamine (Aniline 2,3-xylidine Mesidine "N-ethylarnine Diphenylamine "N phenylcyclohexylamine 'N-phenylallylamine l naphthylamine "B biphenyIamine Benzylamine 'Phe'nethylamine 1 -naphthalenemethylamine 'N-methylb'enzylamine "Examples of diamidolethers iprepared-acc rdirig to the :invention from ran iappropriate hydrocarbon =ar'nine and u-chlorophenylacetyl chloride or the appropriately ar- "substituted chloride are'thelfo'llowing:

e N ikfimethylphenylacetamide) u,u.' OXybiS (N-a'myl-Nephen'yl-4 tolylacetamide) a,u"-Oxybis('N tert-dodecyl-3-nitrophenylacetafnide) a, a Oxyb is (N-cyclohexylphenylacetamide) "11,0? Oxybi's(N,N dibenzyl 4 chloro 3 n itrophenyl- 'u,d"-Ox'ybis (N;N-di-2-butenylpheny1acetamide) a,a'-OXybis(N,N dicyclohexylphenylacetamide) u,a"-'OXy-bis[N-(4 tert butylphenyl)phenylacetamidel I a,a'-O) ybis(N propargylphenylacetamide) "'Z-m'thoxyethylamine Bis(2-ethoxyethyl) amine N,N-bu'tyl-2-propoxyethylamine Bis-4-'( Z-ethylhexyloxy)butylamine N-eycloheXyl-2-methoXyethylamine N-benzyl-Z-decyloxymethylamine "N- ('4-iso'amyloxybutyl) allylamine Still another class of presently useful amines includes: N,N-alkylenediamines such as N,N-dimethylethylenediamine, N,N-diamylpropylenediamine, N,N-dibutyl-'N- ethyl-'1,3-diamidopropane, etc.

Furfurylarnine, difurfurylamine or mixed secondary 'fur'furyl amines react as do the aboveamines to give the present diamido ethers. Thus, furfurylarnine and a-chlo "rophenylacetyl 1 chloride gives u,a'-0XybiS (N-furfurylphenylacetamide), difurfurylamirie and u-chloro-4-tolylacetyl chloride gives a,a-oxybis(N,N difurfuryl-4-tolylacetam= ide), N-(Z-ethoxyethyl)furfurylamine and a-ChlOIO-4- chlor'ophenylacetyl chloride gives a,a-oxybis(N-2-ethoxyethyl-N-furfuryl-4-chlorophenylacetamide) and N-phenylfurfurylamine with 3,4-dichlorophenylacetyl chloride gives ot,a.' oxybis (N amyl-N-furfuryl-3,4-dichlorophenylacetamide).

Heter'ocyclic nitrogen compounds having an unsubstituted N-liy'drogen atom and containing from 4.to' 9 carbon atoms react as do the above primary or secondary amines. Thus, qt-chlorophenylacetyl chloride and morpholine condense to give a,a'-oxybis-[N-(phenylacetyl)morpholinel; similarly, pipefidine and 2-tolylacetyl chloride give actoxybisEN- (2 -tolylacetyl)piperidine]; Pyrrol and fl-chloroplien'ylacetyl chloride give a, oxybis[N-(4-clilofophenylacetyl)pyrrolel; and pyrrolidine with 3-nitrophenylacetyl chloride yields a,ot-oxybis[N-(3-nitrophenyl-acetyl) pyrrolidine].

Reaction of the acyl chlorides with the primary or secondary amines to yield the present diamido ethers takes place readily by simply mixing the two reactants in aqueous' alkaline media and allowingthe reaction mixture to stand until the diamido ethers are formed. Depending upon the nature of the individual acyl halide, amine and aqueous alkali. the condensation reaction may occur under Varying conditions of temperature and pressure. For optimum yields, it is advantageous in many instances to apply external cooling in order to prevent orto minimize possible side reactions. Aqueous alkaline media which may be employed include alkali metal and alkaline earth metal hydroxides, e. g., sodium, potassium, lithium, calcium or magnesium hydroxide; basically reacting salts .thereof such as sodium carbonate, potassium acetate, etc.

Inasmuch as molecular equivalents of the acyl chloride and the primary or secondary amineare involved in the formation of the present condensation product, it is advantageous to employ stoichiometric proportions of these two reactants, as well as of the aqueous alkali. Although an extraneous solvent or diluent is often useful, the reaction may be effected in the absence of such solvents or diluents especially if the" temperature of the reaction mixture is controlled by external cooling. Carbon tetrachloride, ether, hexachloroethane, hexane and kerosene are examples of useful diluents. As hereinbefore stated, the optimum temperatures amployed will vary with the individual nature of the reactant and alkaline agent as well as with the presenceof any extraneous, inert diluent; but generally they range'from, say, minus 20 C. to the refluxing temperature of the reaction mixture.

The present diamido ethers are stable, well-defined products which range from high boiling liquids to crystalline solids. They are generally useful as biological toxicants, particularly as insecticides, fungicides and herbicides.

The present invention is further illustrated, but not limited, by the following examples:

Example 1 Into 150 ml. of carbon tetrachloride there was placed 19.4 g. (0.2 mole) of diallylamine. The resulting mixture was cooled to below minus 10 C. and 42 ml. of a.

chloride and the washings combined with the organic layer. The combined material was then washed with dilute hydrochloric acid, sodium bicarbonate and Water. Distillation of the washed material gave 46 g. (88% theoretical yield) of the substantially pure a,a-oxybis(N,N-

Percent O Percent N.;

diallylphenylacetamide), B. P. l92-198 C./ 28 n 1.5350, and analyzing as follows:

Found Calcd. for

75. 35 75. 8 Percent H 7. 68 7. 22

Percent C I -The a,a', oxybis(N,N diallylphenylacetamide) was found to give a kill of milkweed bugs (Oncepeltus) at a 1.0% concentration and to inhibit entirely the growth of M. pyogenes v-ar. aureus at an 0.1% concentration.

Example 2 filtered 011? and recrystallized from absolute ethanol to give 20 g. of the white, crystalline a,a'-oxybis(N-furfurylphenylacetamide), M. P. 99 -100 C. and analyzing as follows:

Calcd. for CuHuOsNt Percent O Percent H Percent; N

Example 3 To acooled (below minus 10 C.) solution of 3-methoxypropylamine there were separately added 26.4 ml. of 20% aqueous sodium hydroxide and-25 g. (0.132 mole) 'of a-chlorophenylacetyl chloride. During the addition the temperature of the mixture was maintained at below minus 10 C. The whole was then brought to room temperature, stirred for one-hour and allowedto stratify. The organic layer which formed was separated, the aqueous layer was washed twice with carbon tetrachloride, and the combined organic layer and washings washed with 5% hydrochloric acid, then with 5% sodium bicarbonate, and finally with water. After stripping the solvent from the washed material, the residue was distilled underpartial vacuum to give 22 g. (73% theoretical yield) of the substantially pure a,a.'-OXybiS (N,-3-methoxypropyl)phenylacetamide] B. P. 16773 C./3 mm., 2 1.5257, and analyzing as Calcd. for CuHuNz 0| Found Percent H 8 The 'a,u oxybis[(N 3-methoxypropyl)phenylacetamide] was 'found to be very effective against the 2-spotted mite at an 0.2% concentration.

Example 4 This example describes the reaction of N,N-diethyl- 1,3-propanediamine with u-chlorophenylacety-l chloride. A solution of 19.5 g. (0.15 mole) of the diam-inc in 100 -ml. of carbon tetrachloride was cooled to below minus ':'ethylaminopropyl) phenylacetamidel B. a Cf/3'"mm.," r55 1'15 1 82, and analyzing as? follows:

grocers "5 bus layer. "'Distiila'tion of the"'eombined material "gave 24 g. "bf "the substantially pure gel-ogiybis'lNK'idi- 11 5 1.5042, "andanalyzing' asfoll'ows:

'5 Found ;Calcd.t'or Found ,oicarer GioHr'uOzN't Cs'rHiNaQs Per'cnt O 102-79 70. 5 i erceut oueh; $76585 F75 -Percent-H il-51 9.01 Percent H. Y 9. 69 I -9.-!46 "BercentN 10. 70 11.00

.fpholine 150 ml. of carbon tetrachloridethere "was added, while 'keepingthe temperature or .tlre'f-solution at belowminus 10 C., first,22.ml. of aqueous sodium hydroxide and then 2018 g.'(0.11 mole) of the acyl chloride. The whole was thenallowed to'attai'n room temperature. The organic layer which formed 'wassepa- '-rated,the aqueous layer'washed twicewith'carbontetrachloride and'the organic material and washings combined. Vl/ashingof thecombined'rnaterial first with dilute hydrochloric acid, then with dilute-sodium bicarbonate 'and finally with water, and removal of .the solvents from the washed product gave'a solid which" upon recrystallization from ether gave 16 g. (67% yield) of the substantially pure oc,a' oxybis [N (phenylacetyl)morpholine], white needles, M. P. 70-71 C. and analyzing 6.59% N, as against 6.62% N, the calculated value for C24H2805N2.

Example 6 To a solution of 10 g. (0.10 mole) of cyclohexylamine in 150 ml. of carbon tetrachloride maintained at minus 10 C. there were separately added, over a 20 minute period, 21.3 ml. (0.106 mole) of aqueous sodium hydroxide and 20 g. (0.106 mole) of phenylacetyl chloride. The solid which formed upon allowing the reaction mixture to come to room temperature was filtered ofl, and the organic layer which formed in the filtrate was separated, and vacuum evaporated to a solid. Purification of the combined solids was effected by dissolving in boiling methanol and cooling. There was thus obtained 20 g. of the white, crystalline a,a-oxybis(N-cyclohexylphenylacetamide), M. P. 139148 C., and analyzing as follows:

Found Calcd. for

CzaHsaOsNz Percent C 75.62 75. 2 Percent H 8. 17 8.03 Percent N 6.16 6.

The a,a'-oxybis(N-cyclo'hexylphenylacetamide) was found to be effective against the fungus Stemphyllium sarcinaeform at a concentration of 100 p. p. m. in spore germination tests.

Example 7 A solution consisting of 10 g. (0.078 mole) of diisobutylamine in 100 ml. of carbon tetrachloride was cooled to minus 10 C. and there was added to it consecutively during a time of 20 minutes 16 ml. of 20% aqueous sodium hydroxide and 15 g. (0.08 mole) of aachlorophenylacetyl chloride. During the addition the temperature of the mixture was kept at below minus 10 C. It was then allowed to attain room temperature. The organic layer was separated, the aqueous layer was twice washed with carbon tetrachloride, and the washings and organic layer combined. After washing the combined material with dilute hydrochloric a'cid, aqueous sodium bicarbon- This product was found "to possess a severe-effect against broadleafed plants when sprayed thereon in an 0.5% concentration.

Example 8 To a solution of 4.4 g. (0. 6 mole) of tert-butylamine in 100 ml. of carbon tetrachloridethere was added separately and with cooling 13- ml.'"of 20% aqueous sodium hydroxide and 12 g. (.064 mole) of phenylacetyl chloride. During the addition the reaction-mixture was maintained eatbelow minus 10 C. It was then allowed tolattain room temperature. "The organic-layer which'formed was separated and washed consecutively with dilute hydrohloficacidQdilute aqueous sodium bicarbonate and water. Removal of the solvent from the washed product by distillationin"vacuogave a white, solid residue... It was recrystallized from ether to yield -oi,afeoxybis(N- -'tert butylphenylacetamide), 'whiteneedles, M. "P. 1 16- "1 17' C., and analyzing '7.1'4% -N as against 714%,

"the calcillated VaIHefOi CfiI-hiOaNa WhatI claim is:

R-CHG ON Y ROHCON/ in which R is selected from the class consisting of the phenyl group and a phenyl group having from 1 to 2 substituents selected from the class consisting of alkyl radicals of from 1 to 5 carbon atoms, the nitro radical, and chlorine, Y taken separately represents a substituent selected from the class consisting of hydrocarbon radicals of from 1 to 12 carbon atoms, alkoxyalkyl radicals of from 2 to 12 carbon atoms, dialkylaminoalkyl radicals of from 4 to 12 carbon atoms, and the furfuryl radical, Y taken separately is selected from the class consisting of hydrogen and Y, and Y and Y taken together with N form a heterocyclic ring structure of from 4 to 5 carbon atoms which ring structure is attached through said N to the remainder of the molecule of which it forms a part.

2. a,ot-Oxybis(N,N-diallylphenylacetamide). 3. a,x-Oxybis(N-furfurylphenylacetamide) 4. u,a-Oxybis (N-3-methoxypropyl)phenylacetamide] 5. a,at'-Oxybis[N (3 diethylaminopropyl)phenylacetamide].

6. a,a-Oxybis (N,N-diisobutylphenylacetamide) 7. The method which comprises contacting in the presence of aqueous alkali, an acyl halide having the formula RCIJHCOCI of from 1 .to 12 carbon atoms, alkoxyalkyl radicals of "from 2 to 12"car bon' atoms, ""clialkylamino'alkyl radicals of from 4 to 12 carbon atoms, and the furfuryl radical,

Y taken separately is selected from the class consisting of hydrogen and Y, and Y and Y taken together with N form a heterocyclic ring structure of from 4 to 5 carbon atoms which ring structure is attached through said N to the remainder of the molecule of Whichitforflls a part, and recovering from the resulting reaction product an amido ether having the formula I i /Y R-CHC ON iniwhich R is selected from the class consisting of the jphenyl group and a'phenyl group having from 1 to 2 substituents selected from the class consisting of alkyl radicals of from 1 to 5 carbon atoms, the nitro radical andjchlorine, Y taken separately represents a substituent of hydrogen and Y,' and Y and Y taken together with N form a heterocyclic ring structure of from 4 to 5 carbon atoms which ring structure is attached through said N to tl1e remainder of the molecule of which it forms a part.

8.; The method which comprises contacting, in thepresence of aqueous alkali, a-chlorophenylace'tyl chloride with diallylamine, in the presence of an aqueous solution of an alkali metal hydroxide and recovering from the resulting reaction product an a,a'-oxybis(N,N-diallylphenylacetamide) a M 9. The method which comprises contacting a-chlorophenylacetyl chloride with N-furfurylamine in the presence of an aqueous solution of an alkali metal hydroxide and recovering from the resulting reaction product an a,a'-oxybis (N-furfurylphenylacetamide).

' 10. The method which comprises contacting a-chlor'ophenylacetyl chloride with 3-methoxyp ropylamine, in the presence of an aqueous solution of an alkali metal hydroxide and recovering from the resulting reaction product a,a-oxybis[ (N-3-rnethoxypropy1)phenylacetamide] 11. The method which comprises contacting'a-chlorophenylacetyl chloride with N,N-diethyl-l,3-propanediamine, in the presence of an aqueous solution of an alkali metal hydroxide and recovering from the resulting reaction product a,a'-oxybis[N-(3-diethylaminopropyl)phenylacetamide] 12. ,The method which comprises contacting a-chloro- I phenylacetyl chloride with diisobutylamine, in the presence of an aqueous solution of an alkali metal hydroxide and recovering from the resulting reaction product a,a'-

oxybis (N,N-diisobutylphenylacetamide) No references cited. 

1. AN AMIDO ETHER HAVING THE FORMULA 